MicroRNAs profiling in malaria and arbovirus coinfection: A systematic review protocol

BACKGROUND: Coinfections between malaria and arboviruses such as Dengue virus (DENV), chikungunya Virus (CHIKV), and Zika virus (ZIKV) represent a significant clinical and public health challenge. The molecular pathogenesis of these coinfections is complex and poorly understood. MicroRNAs (miRNAs) are key regulators of gene expression and play a crucial role in the host response to infection. A comprehensive profile of miRNAs implicated in malaria-arbovirus coinfection could provide novel insights into disease mechanisms and reveal new targets for improved management and therapeutic strategies. METHODS: The review will be conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy will be executed in electronic databases (PubMed/MEDLINE, Scopus, Web of Science, Embase, CENTRAL, CINAHL) from January 2000 onwards, with no language restrictions. Grey literature sources will also be searched. Included study designs will comprise observational studies (cohort, case-control, cross-sectional) and clinical trials reporting primary data on miRNA expression. Two independent reviewers will screen records, extract data, and assess the risk of bias using appropriate tools (ROBINS-I, ROB-2, NIH tools). Data on study characteristics, patient demographics, confirmation of coinfection, miRNA profiling techniques, and differentially expressed miRNAs will be extracted. Given anticipated heterogeneity, a narrative synthesis will be performed. The strength of the evidence will be assessed using the GRADE approach. CONCLUSION: This systematic review will provide comprehensive evidence on miRNA expression patterns associated with malaria-arbovirus coinfections. The findings will advance understanding of coinfection pathogenesis and identify potential biomarkers for improved diagnostics and therapeutics. It will also pioneer an exploration of cross-kingdom gene regulation by plant-derived miRNAs, establishing a foundation for future functional validation studies. Additionally, the miRNA profiles identified may provide foundations for developing novel therapeutic approaches, including nanoparticle-based delivery systems. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: PROSPERO CRD42024600379.